Diagnostic Journey Late-onset Pompe Disease

The signs and symptoms of late-onset Pompe disease can vary from person to person.

Because it is such a rare disease with symptoms that mimic many other more common disorders, LOPD can be challenging to identify. Because of its progressive nature, diagnosing LOPD as early as possible is important so that the appropriate disease management and care can begin as soon as possible.

  • Doctors use a variety of tests to investigate patients’ symptoms, rule out other diseases, and arrive at a diagnosis
  • One of the big challenges in diagnosing Pompe disease is that many of its symptoms are shared with other diseases

THE DIAGNOSTIC JOURNEY

Getting diagnosed with Pompe disease can be a long and complicated process. It often involves visiting several different doctors and having a variety of tests because symptoms affect many areas of the body. Usually doctors need to first rule out other more common disorders that share similar symptoms with Pompe disease.

Here are some tests that your doctor may perform if it is suspected that you have Pompe disease.

  • The level of muscle weakness and how you are able to function physically may be tested
  • You may be asked to give blood to test for some substances in the blood that are indicators of muscle function and damage
    • A certain chemical, creatine kinase (also known as CK or CPK), may be higher than normal in many people with the disease
    • Other enzymes your doctor may test for are called AST (aspartate transaminase) and ALT (alanine transaminase)
  • Your doctor might perform tests to determine how well you are breathing while you are sitting and lying down
  • Other tests that your doctor may perform include a urine test (urinalysis), muscle imaging/biopsy, sleep tests, electrocardiogram (ECG), and/or chest x-ray
    • Urinalysis can detect increased levels of glucose tetrasaccharide (Glc4), a substance that correlates with the extent of glycogen accumulation in the muscles
    • Muscle imaging and biopsy can detect patterns of abnormalities such as muscle breakdown (atrophy) and fat infiltration (via MRI), or for the presence of vacuoles (glycogen-filled pockets via biopsy), although biopsy cannot always definitively diagnose LOPD
    • Sleep tests may be ordered to determine breathing (respiratory) function and/or weakness if a person complains of excessive daytime sleepiness, morning headaches, or if sleep apnea (brief, repeated periods of interruptions in breathing during sleep) has been observed
    • Chest x-rays can detect enlargement of the heart (cardiomegaly) and an ECG can identify abnormalities in the heart’s electrical activity

The tests above can suggest a diagnosis of LOPD, but only 2 tests can diagnose LOPD definitively: a blood test for enzyme activity and a genetic test.

  • Enzyme assay: This test detects the amount of GAA enzyme activity a patient has. Recall that Pompe disease is caused by a genetic defect in a gene that makes the enzyme called acid alpha-glucosidase, or GAA. The result of this defect, or mutation, is that there is an absence or deficiency of this enzyme.1 Infants with a very severe form of the disease have very little to no enzyme activity (<1% of normal levels), but people with LOPD can have anywhere from 2% to 40% of normal enzyme activity.
  • Genetic testing: A blood or saliva test can also provide more information about the specific genetic defect in the GAA gene that causes less enzyme to be produced; this is called mutation analysis. Depending on how much GAA enzyme activity is remaining, a genetic analysis may be useful for some patients when GAA enzyme activity is near normal levels. If clinical judgment dictates, your doctor may also order a multigene test panel to investigate the possibility of Pompe disease and other inherited disorders simultaneously.
Get more information on testing options here.

DISEASES WITH SIMILAR SYMPTOMS AND THE DIFFERENTIAL DIAGNOSIS

One reason that LOPD is so difficult to diagnose is that the symptoms mimic or are similar to many other diseases like it. Therefore, in certain difficult-to-diagnose diseases, doctors must first rule out other diseases to make a definitive diagnosis; this is called making a differential diagnosis. The figure below is a list of other disorders that mimic Pompe disease, particularly LOPD, and are part of the differential diagnosis of LOPD.

DISORDERS THAT MIMIC LOPD

The symptoms listed below are not an exhaustive list and may not be inclusive of all symptoms that someone with these diseases may encounter.

Abnormal walking

Decreased muscle tone (in childhood)

Difficulty breathing

Difficulty swallowing

Elevated CK

Enlarged liver

Enlarged liver (in childhood)

Evidence of diseased muscle

Heart muscle disease

Minor muscle weakness

Muscle cramps when exercising

Muscle weakness

Muscle weakness, decreased muscle tone

Muscle weakness (lower limbs)

Muscle weakness/ shrinking (atrophy)

Pain or fatigue after exercise

Progressive muscle weakness

Progressive muscle weakness in lower limbs

Progressive muscle weakness in the shoulders